伏隔核胆碱能神经元在线索诱导的海洛因复吸中的作用  

Role of cholinergic neurons in nucleus accumbens on cues-induced heroin relapse

作　　者：朱华强[1,2] 刘惠芬[1,2] 赖苗军[1,2] 陈为升[1,2] 周文华[1,2] 

机构地区：[1]宁波市微循环与莨菪类药研究所 [2]宁波大学行为神经科学研究中心,浙江宁波315010

出　　处：《中国药理学与毒理学杂志》2012年第3期288-293,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点基础研究发展计划资助(973计划)(2009CB522008);国家自然科学基金(30870824);浙江省人才计划资助项目(2010R10058);宁波市自然科学基金(2009A610123)~~

摘　　要：目的比较不同的二醋吗啡(海洛因)戒断时间对于环境线索(CC)或条件性线索(CS)诱导的大鼠复吸行为的影响,并探讨伏隔核胆碱能神经元可能的调节作用。方法 SD大鼠进行海洛因自身给药训练,每天4 h,连续14 d,建立海洛因自身给药模型。随后置饲养笼自然戒断,随机分为第1天CC(d 1CC)组、d 14 CC组、d 1 CC+CS组和d 14 CC+CS组。测定有效鼻触次数,免疫组化双标法检测伏隔核(NAc)壳部和NAc核部胆碱乙酰转移酶(ChAT)与c-Fos共表达的水平。结果海洛因自身给药大鼠随着戒断时间延长,CC诱导的海洛因觅药行为的恢复,即d 14 CC组与d 1 CC组比较,有效鼻触数明显增加(P<0.05);海洛因自身给药大鼠相同时间戒断后,不同线索诱导的海洛因觅药行为的恢复,即d 1 CC+CS组与d 1 CC组比较,以及d 14 CC+CS组与d 14 CC组比较,有效鼻触数均明显增加(P<0.05)。同时,在NAc壳部,与d 1 CC组比较,d 14 CC组大鼠的ChAT,c-Fos,ChAT+c-Fos免疫阳性细胞数分别为114±9,15±6,(13±5)个,ChAT+c-Fos占ChAT百分比为(11±4)%,明显增加(P<0.05);在NAc壳部和NAc核部,与d 1 CC组比较,d 1 CC+CS组大鼠的上述表达没有差异;在NAc壳部和NAc核部,与d 14 CC组比较,d 14 CC+CS组的ChAT,ChAT+c-Fos免疫阳性细胞数均明显减少(P<0.05)。结论随着戒断时间的延长,CC诱导的海洛因觅药行为的增加,可能与NAc壳部胆碱能神经元的激活增多有关;而CS诱导的海洛因觅药行为的增加,可能与NAc壳部和核部胆碱能神经元的激活减少有关。OBJECTIVE To investigate the effect of different durations of withdrawal on dia- morphine （heroin） seeking behaviors induced by drug-associated contextual cue （CC） or condi- tioned stimuli （CS） and its possible mechanism. METHODS After heroin self-administration for 14 d, rats were left in their home cages for 1 or 14 d of withdrawal and randomly divided into groups. After 1 d or 14 d of withdrawal, extinction responses of nose-pokes induced by CC were evaluated in d 1 CC group and d 14 CC groups. Heroin seeking behaviors induced by CC and CS were measured in d 1 CC ＋ CS group and d 14 CC ＋ CS groups. The double labeled expression of choline acetyltransferase （CHAT） and c-fos in the nucleus accumbens （NAc） core and shell were assayed by immunohistochemistry. RESULTS The behavior results showed that after 14 d with- drawal, rats emitted significantly more active nose-poking responses during a test of heroin-seeking induced by CC compared with 1 d withdrawal. On the d 1 or d 14 of withdrawal, the active nose-po- king responses of rats induced by CC ＋ CS were all higher than those induced by CC. Compared with 1 d CC group, the number of CHAT, c-Fos, and ChAT ＋ c-Fos immuno-positive neurons and the per- centage of ChAT ＋ c-Fos neurons in ChAT-labeled neurons in the NAc shell of d 14 CC group were 114±9, 15 _＋ 6 and 13 -5 and （ 11±4 ） %, which obviously increased, respectively （ P 〈 0.05 ）. Compared with d 1 CC group, the expression in the NAc shell and core of d 1 CC ＋ CS group had no difference. Compared with d 14 CC group, the number of ChAT and ChAT ＋ c-Fos immuno-positive neurons in the NAc shell and core of d 14 CC ＋ CS decreased, respectively （P 〈 0.05 ）. CONCLUSION Prolonged duration of withdrawal increases both CC or CS-induced heroin-seeking. The increased cholinergic neuron activity in the NAc shell is associated with CC-induced drug-seeking while decreasing cholinergic neuron activity in the NAc shell and core is related to CS-induced drug-seeking.

关 键 词：乙酰胆碱 海洛因 伏隔核 复吸 

分 类 号：R96[医药卫生—药理学]